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Independent Determinants of Second Derivative of the Finger Photoplethysmogram among Various Cardiovascular Risk Factors in Middle-Aged Men

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Sdptg1

  1. 1. 1211 Hypertens Res Vol.30 (2007) No.12 p.1211-1218 Original Article Independent Determinants of Second Derivative of the Finger Photoplethysmogram among Various Cardiovascular Risk Factors in Middle-Aged Men Toshiaki OTSUKA1), Tomoyuki KAWADA1), Masao KATSUMATA1), Chikao IBUKI2), and Yoshiki KUSAMA3) The second derivative of the finger photoplethysmogram (SDPTG) has been used as a non-invasive exam- ination for arterial stiffness. The present study sought to elucidate independent determinants of the SDPTG among various cardiovascular risk factors in middle-aged Japanese men. The SDPTG was obtained from the cuticle of the left-hand forefinger in 973 male workers (mean age: 44 ± 6 years) during a medical checkup at a company. The SDPTG indices (b/a and d/a) were calculated from the height of the wave components. Mul- tiple logistic regression analyses revealed that the independent determinants of an increased b/a (highest quartile of the b/a) were age (odds ratio [OR]: 1.12 per 1-year increase, 95% confidence interval [CI]: 1.09– 1.15), hypertension (OR: 1.65, 95% CI: 1.03–2.65), dyslipidemia (OR: 1.51, 95% CI: 1.09–2.09), impaired fast- ing glucose/diabetes mellitus (OR: 2.43, 95% CI: 1.16–5.07), and a lack of regular exercise (OR: 2.00, 95% CI: 1.29–3.08). Similarly, independent determinants of a decreased d/a (lowest quartile of the d/a) were age (OR: 1.11 per 1-year increase, 95% CI: 1.08–1.14), hypertension (OR: 3.44, 95% CI: 2.20–5.38), and alcohol intake 6 or 7 days per week (OR: 2.70, 95% CI: 1.80–4.06). No independent association was observed between the SDPTG indices and blood leukocyte count or serum C-reactive protein levels. In conclusion, the SDPTG indices reflect arterial properties affected by several cardiovascular risk factors in middle-aged Japanese men. The association between inflammation and the SDPTG should be evaluated in further stud- ies. (Hypertens Res 2007; 30: 1211–1218) Key Words: arterial stiffness, cardiovascular preventive medicine, finger photoplethysmogram, risk factors mainly in Japan, as a non-invasive method for pulse wave analysis (5). The indices calculated from the SDPTG wave- Introduction forms are reported to correlate closely with both the distensi- The measurement of arterial stiffness has become an impor- bility of the carotid artery (6) and the central augmentation tant diagnostic modality in various clinical and epidemiolog- index (AIx) (5), suggesting the SDPTG indices may be a sur- ical settings, because increased arterial stiffness is associated rogate measure of arterial stiffness. Several previous studies with an increased risk of cardiovascular disease (CVD) (1–4). showed that the SDPTG indices are associated with age (5, 7– The second derivative of the finger photoplethysmogram 10), blood pressure (BP) (7, 8, 10), the estimated risk of cor- (SDPTG), which is obtained from the double differentiation onary heart disease (8), and the presence of atherosclerotic of the finger photoplethysmogram (PTG), has been used, disorders (11). However, there is still less information on the From the 1)Environmental Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 2)Cardiovascular Center, Nippon Medical School Chiba-Hokusoh Hospital, Chiba, Japan; and 3)Department of Internal Medicine and Cardiology, Nippon Medical School Tama-Nagayama Hospi- tal, Tokyo, Japan. Address for Reprints: Toshiaki Otsuka, M.D., Environmental Medicine, Graduate School of Medicine, Nippon Medical School, 1–1–5 Sendagi, Bun- kyo-ku, Tokyo 113–8602, Japan. E-mail: otsuka@nms.ac.jp Received June 8, 2007; Accepted in revised form July 25, 2007.
  2. 2. 1212 Hypertens Res Vol. 30, No. 12 (2007) SDPTG than on other modalities to measure arterial stiffness. Moreover, to our knowledge, there are no reports on the asso- 36 y.o. 50 y.o. ciation between the SDPTG and various cardiovascular risk factors including inflammation, excessive alcohol drinking, and a lack of regular exercise. The present study is a cross-sectional evaluation of the PTG independent determinants of the SDPTG among various risk factors for CVD in middle-aged Japanese men. Methods Study Population SDPTG This study was conducted during an annual medical checkup 0 at a company that develops precision equipment in Kana- gawa, Japan, in 2005. A total of 1,074 male employees 0.2 s between 35 and 60 years of age received the medical checkup. All employees were engaged in daytime, desk work. Among Fig. 1. Representative waveforms of PTG (top) and SDPTG them, the following were excluded: those on medication for (bottom) in a 36-year-old man and a 50-year-old man who hypertension, dyslipidemia, or diabetes mellitus (n= 60); and participated in the present study. The SDPTG consists of five those with acute or chronic inflammatory disorders including waves named a, b, c, d, and e. The a and b waves are in the infectious disease (n= 8), the presence or history of CVD early systolic phase, the c and d waves in the late systolic (n= 5), or an incomplete recording of the SDPTG (n= 2). In phase, and the e wave in the diastolic phase of the PTG. The addition, subjects with C-reactive protein (CRP) ≥ 10.0 mg/L b and d waves in participants who were 50 years of age were (n= 15) or leukocyte count ≥ 10.0 × 109/L (n= 11) were also shallower and deeper, respectively, than in those who were excluded because the presence of an infection or inflamma- 36 years of age. PTG, finger photoplethysmogram; SDPTG, tion was suspected. Finally, 973 subjects participated in the second derivative of the finger photoplethysmogram. present study. The study protocol was approved by the ethics committee of Nippon Medical School, and all participants gave their written informed consent. each subject’s arm circumference. The first and fifth Korot- koff sounds were recorded to determine the systolic and dias- tolic BP, respectively. Biochemical and Physical Measurements Hypertension was defined as systolic BP ≥ 140 mmHg and/ All anthropometric and hemodynamic measurements and or diastolic BP ≥ 90 mmHg. Dyslipidemia was defined as blood sampling were conducted between 9 AM and 11 AM in LDL cholesterol ≥ 140 mg/dL, triglycerides ≥ 150 mg/dL, a temperature-controlled room maintained at 22±2°C. Blood and/or HDL cholesterol < 40 mg/dL according to the updated samples were obtained from the antecubital vein after over- Japanese Atherosclerosis Society criteria (13). Obesity was night fasting. Standard enzymatic methods were used to mea- defined as body mass index ≥ 25 kg/m2. Impaired fasting glu- sure the serum total cholesterol, triglycerides, and plasma cose (IFG)/diabetes mellitus (DM) was defined as fasting glucose with an automated analyzer (Model 7170, Hitachi plasma glucose ≥ 110 mg/dL. Current smoking was defined High-Technologies, Tokyo, Japan). The serum high-density as regularly smoking during the previous 12 months. The fre- lipoprotein (HDL) cholesterol was measured using the direct quency of alcohol intake was categorized as follows: 0 to 1 method. The low-density lipoprotein (LDL) cholesterol level day per week, 2 to 5 days per week, or 6 to 7 days per week. was calculated by using Friedewald’s formula in 962 partici- Regular exercise was defined as continuous exercise for at pants with serum triglyceride levels < 400 mg/dL. Blood leu- least 15 min 2 days or more per week for at least 1 year. Ele- kocytes were counted by an automatic cell counter (SE9000, vated leukocyte count and CRP were defined as the highest Sysmex, Kobe, Japan). The serum CRP level was measured quartile of each parameter (≥ 6.3 × 109/L and ≥ 0.6 mg/L, using a latex turbidimetric immunoassay kit (LPIA CRP-H, respectively). Mitsubishi Kagaku Iatron, Tokyo, Japan) with an automated analyzer (Model 7170). The lower detection limit of this SDPTG Measurement assay is 0.1 mg/L. The intra-assay coefficient of variation is reported to be ≤ 3.4% (12). The systolic and diastolic BP were The SDPTG was recorded in the sitting position using an measured twice by well-trained staff members using the right SDP-100 instrument (Fukuda Denshi, Tokyo, Japan), with the arm of a seated subject, after at least 5 min of rest, using a subject having rested for at least 5 min after BP measurement. mercury sphygmomanometer with the optimal cuff size for A transducer was placed on the cuticle of the forefinger of the
  3. 3. Otsuka et al: SDPTG and Risk Factors for CVD 1213 left hand at the same height as the subject’s heart. The signal Table 1. Characteristics of the Study Subjects (n=973) of the blood volume changes in the peripheral circulation, Age (years) 44±6 which indicated the PTG, was sent to the SDP-100. The PTG 35–40 (%) 35.1 describes the changes in the absorption of light by hemoglo- 41–50 (%) 49.9 bin using a waveform according to the Lambert-Beer law 51–60 (%) 15.0 (14). The PTG measurement methodology is described in Height (m) 1.71±0.06 detail elsewhere (15). Multiple waveforms of the PTG were Body mass index (kg/m2) 23.3±2.9 obtained during 5-s recordings. The PTG waveforms were Obesity (%) 23.5 then averaged, and the double differentiation of the averaged Heart rate (bpm) 69±10 PTG (i.e., SDPTG) was performed automatically by the Systolic BP (mmHg) 119±13 device. Diastolic BP (mmHg) 76±10 Representative waveforms of the PTG and SDPTG in 2 Hypertension (%) 11.3 participants, aged 36 and 50 years old, are described in Fig. 1. Total cholesterol (mg/dL) 200±32 The SDPTG consists of four waves in systole (a, b, c, and d Triglycerides (mg/dL) 115±106 waves) and one wave in diastole (e wave). The a and b waves HDL cholesterol (mg/dL) 56±14 on the SDPTG are included in the early systolic phase of the LDL cholesterol (mg/dL) (n=962) 122±28 PTG, while the c and d waves are included in the late systolic Dyslipidemia (%) 43.5 phase. The height of each wave from the baseline was mea- Fasting plasma glucose (mg/dL) 91±11 sured, with the values above the baseline being positive and IFG/DM (%) 4.1 those under it negative. The ratios of the height of the b and d Leukocyte count (× 109/L) 5.6±1.3 waves to that of the a wave (b/a and d/a) were calculated from CRP (mg/L) 0.3 (0.2, 0.6) the SDPTG waveform. These ratios were used as the SDPTG Current smoking (%) 28.5 indices in this study, according to the report by Takazawa et Family history of CVD (%) 23.0 al. (5). The acceptable reproducibility of these indices has Lack of regular exercise (%) 79.1 been reported (11, 16). An increased b/a and a decreased d/a Frequency of alcohol intake have been thought to represent increased arterial stiffness (5). 0 to 1 day per week (%) 39.2 2 to 5 days per week (%) 37.2 Statistical Analysis 6 to 7 days per week (%) 23.6 SDPTG index Continuous variables were expressed as mean±SD, mean b/a −0.64±0.11 (95% confidence interval), or median (interquartile range), as d/a −0.26±0.12 appropriate. Categorical data were expressed as percentages. Since the values of CRP were skewed to the left, its log-trans- The value of CRP is expressed as the median (interquartile formed data were used for a simple correlation analysis. All range). Other values are the mean±SD or % of total. BP, blood analyses were conducted using the SPSS software program pressure; CRP, C-reactive protein; CVD, cardiovascular disease; DM, diabetes mellitus; HDL, high-density lipoprotein; IFG, version 11.0.1 (SPSS, Chicago, USA). Pearson’s moment impaired fasting glucose; LDL, low-density lipoprotein; correlation coefficient was used to evaluate the simple corre- SDPTG, second derivative of a finger photoplethysmogram. lations between the SDPTG indices and the clinical parame- ters. Differences in the mean SDPTG indices between the groups with and without each cardiovascular risk factor were compared using an analysis of covariance with age, height, body mass index, systolic BP, diastolic BP, total cholesterol, and heart rate as covariates. To detect independent determi- triglycerides, HDL and LDL cholesterol, and fasting plasma nants of the SDPTG indices, logistic regression analyses were glucose were within the normal ranges. While IFG/DM was performed. First, the odds ratios of each cardiovascular risk present in less than 5% of study subjects, dyslipidemia was factor for an increased b/a (≥ −0.56, highest quartile of the b/ present in more than 40%. The mean leukocyte count was 5.6 a) and a decreased d/a (≤ −0.34, lowest quartile of the d/a) × 109/L, and the median CRP level was 0.3 mg/L. The preva- were calculated using univariate analysis. The variables with lence among subjects who did not exercise regularly or who a p value of less than 0.10 in that analysis were entered into drank alcohol 6 to 7 days per week was 79.1% and 23.6%, multivariate analysis. All statistical tests were two-sided, and respectively. a p value of less than 0.05 was considered significant. Correlations between the SDPTG indices and clinical parameters are noted in Table 2. Both SDPTG indices corre- lated substantially with age. Height, heart rate, total and LDL Results cholesterol, fasting plasma glucose, and leukocyte count also The baseline characteristics of the study subjects are shown in significantly correlated with both SDPTG indices. The sys- Table 1. The mean age was 44±6 years. The mean values of tolic and diastolic BP appeared to correlate considerably bet-
  4. 4. 1214 Hypertens Res Vol. 30, No. 12 (2007) Table 2. Correlation Coefficients of the SDPTG Indices with the Clinical Parameters b/a d/a r p value r p value Age 0.40 <0.001 -0.41 <0.001 Height −0.23 <0.001 0.17 <0.001 Body mass index −0.02 0.470 −0.08 0.019 Systolic BP 0.10 0.003 −0.27 <0.001 Diastolic BP 0.09 0.004 −0.29 <0.001 Heart rate −0.17 <0.001 0.09 0.007 Total cholesterol 0.09 0.005 −0.10 0.002 Triglycerides 0.02 0.583 −0.05 0.159 HDL cholesterol −0.03 0.425 −0.02 0.475 LDL cholesterol 0.10 0.003 −0.07 0.035 Fasting plasma glucose 0.09 0.007 −0.10 0.002 Leukocyte count 0.09 0.006 −0.08 0.011 log CRP 0.02 0.448 −0.07 0.039 BP, blood pressure; CRP, C-reactive protein; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SDPTG, second derivative of a finger photoplethysmogram. b/a -0.58 ** -0.60 * -0.62 * ** -0.64 -0.66 -0.68 Obesity Hypertension Dyslipidemia IFG / DM Elevated leukocyte count b/a -0.58 -0.60 ** -0.62 -0.64 ** -0.66 -0.68 Elevated CRP Current smoking Family history Regular exercise Alcohol intake of CVD Fig. 2. Comparison of the mean b/a between the groups with and without each cardiovascular risk factor. The mean values were adjusted for age, height, and heart rate. Error bars indicate 95% confidence intervals. CRP, C-reactive protein; CVD, car- diovascular disease; DM, diabetes mellitus; IFG, impaired fasting glucose. *p< 0.05, **p< 0.01. Alcohol intake: (−), 0 to 1 day per week; (+), 2 to 5 days per week; (++), 6 to 7 days per week. ter with the d/a than with the b/a. A weak correlation between and current smoking, while it was significantly lower in the the CRP level and the d/a was observed, but no correlation group with obesity and regular exercise than in the group with the b/a was observed. without. On the other hand, the d/a was significantly lower in The differences in the adjusted means of the b/a and d/a the group with hypertension and dyslipidemia than in the between the groups with and without each cardiovascular risk group without. Alcohol intake 6 to 7 days per week was sig- factor are shown in Figs. 2 and 3, respectively (detailed val- nificantly associated with a decreased d/a. ues not shown). The b/a was significantly higher in the group The odds ratios of each cardiovascular risk factor for an with hypertension, dyslipidemia, elevated leukocyte count, increased b/a and a decreased d/a are noted in Tables 3 and 4,
  5. 5. Otsuka et al: SDPTG and Risk Factors for CVD 1215 d/a -0.23 * -0.27 *** -0.31 -0.35 Obesity Hypertension Dyslipidemia IFG / DM Elevated leukocyte count d/a -0.23 ** -0.27 -0.31 -0.35 Elevated CRP Current smoking Family history Regular exercise Alcohol intake of CVD Fig. 3. Comparison of the mean d/a between the groups with and without each cardiovascular risk factor. The mean values were adjusted for age, height, and heart rate. Error bars indicate 95% confidence intervals. CRP, C-reactive protein; CVD, car- diovascular disease; DM, diabetes mellitus; IFG, impaired fasting glucose. *p< 0.05, **p< 0.01 vs. (+) and p< 0.001 vs. (−), ***p< 0.001. Alcohol intake: (−), 0 to 1 day per week; (+), 2 to 5 days per week; (++), 6 to 7 days per week. Table 3. Odds Ratio of Each Cardiovascular Risk Factor for an Increased b/a Univariate Multivariate Variables Odds ratio (95% CI) p value Odds ratio (95% CI) p value Age (per 1-year increase) 1.13 (1.10–1.16) <0.001 1.12 (1.09–1.15) <0.001 Height (per 0.01-m increase) 0.93 (0.90–0.95) <0.001 0.94 (0.91–0.97) <0.001 Heart rate (per 1-bpm increase) 0.97 (0.96–0.99) 0.003 0.96 (0.94–0.98) <0.001 Obesity 0.84 (0.59–1.20) 0.337 — Hypertension 1.81 (1.19–2.76) 0.006 1.65 (1.03–2.65) 0.038 Dyslipidemia 1.70 (1.27–2.28) <0.001 1.51 (1.09–2.09) 0.014 IFG/DM 3.24 (1.71–6.13) <0.001 2.43 (1.16–5.07) 0.018 Elevated CRP 0.97 (0.70–1.35) 0.852 — Elevated leukocyte count 1.34 (0.97–1.85) 0.079 0.92 (0.63–1.34) 0.650 Current smoking 1.47 (1.08–2.01) 0.016 1.27 (0.89–1.83) 0.189 Family history of CVD 1.23 (0.88–1.72) 0.234 — Lack of regular exercise 1.54 (1.05–2.28) 0.028 2.00 (1.29–3.08) 0.002 Alcohol intake* 2 to 5 days per week 1.17 (0.83–1.64) 0.365 — 6 to 7 days per week 1.27 (0.87–1.85) 0.221 — Variables with a p value of less than 0.10 in the univariate analysis were entered into the subsequent multivariate analysis. *Zero to 1 day per week as a reference. CI, confidence interval; CRP, C-reactive protein; CVD, cardiovascular disease; DM, diabetes mellitus; IFG, impaired fasting glucose. respectively. Multiple logistic regression analyses revealed nants of a decreased d/a were age, height, hypertension, and the independent determinants of an increased b/a to be age, an alcohol intake of 6 to 7 days per week. Hypertension height, heart rate, hypertension, dyslipidemia, IFG/DM, and a appeared to more strongly influence the d/a than the b/a (odds lack of regular exercise. Similarly, the independent determi- ratio: 1.65 for the b/a and 3.44 for the d/a).
  6. 6. 1216 Hypertens Res Vol. 30, No. 12 (2007) Table 4. Odds Ratio of Each Cardiovascular Risk Factor for a Decreased d/a Univariate Multivariate Variables Odds ratio (95% CI) p value Odds ratio (95% CI) p value Age (per 1-year increase) 1.13 (1.11–1.16) <0.001 1.11 (1.08–1.14) <0.001 Height (per 0.01-m increase) 0.95 (0.93–0.98) <0.001 0.96 (0.93–0.99) 0.003 Heart rate (per 1-bpm increase) 0.99 (0.98–1.01) 0.473 — Obesity 1.06 (0.75–1.49) 0.759 — Hypertension 4.02 (2.68–6.05) <0.001 3.44 (2.20–5.38) <0.001 Dyslipidemia 1.50 (1.12–2.01) 0.007 1.29 (0.93–1.80) 0.131 IFG/DM 1.90 (0.98–3.67) 0.056 0.96 (0.47–1.97) 0.908 Elevated CRP 1.32 (0.96–1.82) 0.090 1.25 (0.87–1.79) 0.228 Elevated leukocyte count 1.28 (0.92–1.77) 0.144 — Current smoking 1.27 (0.93–1.74) 0.140 — Family history of CVD 1.20 (0.86–1.69) 0.291 — Lack of regular exercise 1.00 (0.70–1.43) 0.980 — Alcohol intake* 2 to 5 days per week 1.24 (0.87–1.77) 0.241 1.33 (0.90–1.96) 0.148 6 to 7 days per week 2.71 (1.87–3.92) <0.001 2.70 (1.80–4.06) <0.001 Variables with a p value of less than 0.10 in the univariate analysis were entered into the subsequent multivariate analysis. *Zero to 1 day per week as a reference. CI, confidence interval; CRP, C-reactive protein; CVD, cardiovascular disease; DM, diabetes mellitus; IFG, impaired fasting glucose. between the SDPTG and age (5, 7–10). The present results therefore support these earlier observations. Discussion Hypertension was significantly associated with both the b/ The novel feature of the present study is to evaluate the inde- a and d/a in the present study, which is also consistent with pendent determinants of the SDPTG among various risk fac- previous reports (7, 8, 10). Elevated BP is thought to increase tors for CVD by means of multiple logistic regression arterial stiffness (17, 18). Therefore, the association of hyper- analysis in a relatively large population. The results indicate tension with the SDPTG in both the present and the previous that several risk factors for CVD, such as age, hypertension, studies is a plausible observation. Importantly, the odds ratios dyslipidemia, IFG/DM, a lack of regular exercise, and exces- of hypertension for a decreased d/a was more than twice that sive drinking (6 to 7 days per week), were significantly asso- for an increased b/a even after adjusting for multiple potential ciated with the SDPTG indices. In contrast, the present study confounders. As mentioned above, the d/a at least partially failed to identify any independent association between the reflects the functional properties of peripheral circulation, SDPTG indices and serum CRP levels or the blood leukocyte which also indicates the peripheral vascular resistance. The count. impact of hypertension on the d/a may therefore be greater The b/a and d/a were used as the SDPTG indices in the than that on the b/a. present study. Because the b wave on the SDPTG is included This study demonstrated, for the first time to our knowl- in the early systolic phase of the PTG, it is only slightly edge, that dyslipidemia was independently associated with affected by the reflected components from the periphery. the b/a. The results of several clinical studies investigating the Imanaga et al. reported that the b/a is correlated with the dis- association between lipid profiles and arterial stiffness are tensibility of the carotid artery (6), a surrogate measure of still controversial (19–22), possibly because of the difference large arterial stiffness. In contrast, because the d wave is in the duration of vascular exposure to the dyslipidemic state included in the late systolic phase of the PTG, it should be (23, 24). However, the relationship between the duration in enhanced by the backward wave from the periphery. Taka- those suffering from dyslipidemia and the SDPTG cannot be zawa et al. reported that the d/a is significantly correlated discussed because this information was not available in the with the central AIx (5), which represents the structural and present study. functional properties of the systemic arterial tree including The present study also showed that other risk factors for the peripheral circulation. CVD such as IFG/DM, a lack of regular exercise, and exces- The present study showed that the SDPTG indices were sive alcohol drinking were independent determinants of an robustly related to age. The SDPTG was originally proposed increased b/a or a decreased d/a. In experimental studies, as an assessment tool for “vascular aging” (5), and a number hyperglycemia (and related hyperinsulinemia and increased of previous studies have shown a considerable association advanced glycation endproducts) and chronic ethanol admin-
  7. 7. Otsuka et al: SDPTG and Risk Factors for CVD 1217 istration were reported to decrease the contents of elastin in 3. Shokawa T, Imazu M, Yamamoto H, et al: Pulse wave the vessel wall and/or to elevate vascular tone (25, 26), which velocity predicts cardiovascular mortality: findings from the in turn increases arterial stiffness. These mechanisms may Hawaii−Los Angeles−Hiroshima study. Circ J 2005; 69: contribute at least partially to the associations between the 259–264. SDPTG and these factors. On the other hand, recent experi- 4. Dolan E, Thijs L, Li Y, et al: Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dub- mental studies showed that exercise had a negligible effect on lin Outcome Study. Hypertension 2006; 47: 365–370. arterial stiffness (27, 28), whereas in human studies regular 5. Takazawa K, Tanaka N, Fujita M, et al: Assessment of exercise is thought to have a favorable effect on arterial prop- vasoactive agents and vascular aging by the second deriva- erties (29–31). The present results showing the association tive of photoplethysmogram waveform. Hypertension 1998; between exercise and the SDPTG indices are in line with the 32: 365–370. results of the human studies. 6. Imanaga I, Hara H, Koyanagi S, Tanaka K: Correlation Recently, numerous studies have indicated that inflamma- between wave components of the second derivative of tion increases arterial stiffness (32–36). However, in the cur- plethysmogram and arterial distensibility. Jpn Heart J rent study the SDPTG indices were not independently 1998; 39: 775–784. associated with the blood leukocyte count or serum CRP lev- 7. Hashimoto J, Watabe D, Kimura A, et al: Determinants of els. Although it is not possible to clearly explain this discrep- the second derivative of the finger photoplethysmogram and brachial-ankle pulse-wave velocity: the Ohasama study. Am ancy, the current results may be influenced by some biases, J Hypertens 2005; 18: 477–485. such as the healthy worker effect, because this study was con- 8. Otsuka T, Kawada T, Katsumata M, Ibuki C: Utility of sec- ducted at a certain company. To our knowledge, no other ond derivative of the finger photoplethysmogram for the reports have investigated the association between the SDPTG estimation of the risk of coronary heart disease in the gen- and inflammation. Further studies are needed to evaluate their eral population. Circ J 2006; 70: 304–310. association in community-based populations. 9. Ohshita K, Yamane K, Ishida K, Watanabe H, Okubo M, This study has some limitations. First, heart rate and height Kohno N: Post-challenge hyperglycaemia is an independent were selected as independent determinants of the SDPTG risk factor for arterial stiffness in Japanese men. Diabet indices. Particularly, an elevated heart rate ameliorates the Med 2004; 21: 636–639. SDPTG indices, although resting tachycardia is thought to be 10. Hashimoto J, Chonan K, Aoki Y, et al: Pulse wave velocity a cardiovascular risk factor (37, 38). These confounders must and the second derivative of the finger photoplethysmogram in treated hypertensive patients: their relationship and asso- be considered when measuring and evaluating the SDPTG. ciating factors. J Hypertens 2002; 20: 2415–2422. However, this limitation is not specific to the SDPTG but is 11. Bortolotto LA, Blacher J, Kondo T, Takazawa K, Safar ME: common to other representative measures of arterial stiffness Assessment of vascular aging and atherosclerosis in hyper- (2). Second, the population of this study consisted of only tensive subjects: second derivative of photoplethysmogram middle-aged Japanese men. Therefore, the present results versus pulse wave velocity. Am J Hypertens 2000; 13: 165– may not extrapolate to other populations including women, 171. the elderly, or other ethnic groups. 12. Roberts WL: CDC/AHA Workshop on Markers of Inflam- In conclusion, the present study showed that several risk mation and Cardiovascular Disease: Application to Clinical factors for CVD, such as age, hypertension, dyslipidemia, and Public Health Practice: laboratory tests available to IFG/DM, a lack of regular exercise, and excessive alcohol assess inflammation-performance and standardization: a drinking, were independently associated with the SDPTG background paper. Circulation 2004; 110: e572–e576. 13. Teramoto T, Sasaki J, Ueshima H, et al: Executive sum- indices in middle-aged Japanese men. 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